The Ly-6 group of alloantigens is one example of cell-surface antigen systems which are encoded by multigene families. At least five distinct Ly-6 antigens named Ly-6A, B, C, D and Th B have been identified by us and others. Decisive progress in the biochemical and serological characterization of these antigens strongly supports our working hypothesis of close structural relationships between the Ly-6 antigens. Direct support is rendered by analysis at the DNA level with the first Ly-6 cDNA probe available, which has confirmed the existence of multiple cross-hybridizing Ly-6DNA sequences in the mouse genome. The other breakthrough was the demonstration in several laboratories, including ours, that Ly-6.A antigens are important modulators allied with T cell activation, thus providing for the first time clues regarding the physiological role of Ly-6 for lymphocytes. In view of these new developments our project on the immunogenetics of Ly-6 will be redefined as follows: we will 1) Analyse the Ly-6A and related genes in detail, 2) Continue cellular immunological studies of Ly-6 using normal cells and cloned cell lines to test the hypothesis that Ly-6 is a signal modulator in cellular activation, 3) Continue the biochemical characterization of Ly-6 proteins to determine glycosylation and phosphorylation status and their form of plasma membrane association, 4) Look for Ly-6 involvement in multimolecular complexes on the cell surface, 5) Following the finding that Ly-6A is selectively induced by interferon, study modulation of Ly-6 antigen and gene expression by lymphokines on T cell, B cells and NK cells and correlate this with functional responses.